DESCRIPTION: (Applicant's Description) One of my academic career goals is to develop molecular and genetic epidemiologic research to identify etiologic factors associated with pigmented lesions, including cutaneous malignant melanoma and multiple primary melanoma (MPM). Determination of susceptibility genes for melanoma can facilitate identification of those at increased risk for disease and may result in increase public and individual efforts of prevention and early detection. The potential impact of these measures is great, as melanoma incidence has reached epidemic proportions and mortality due to melanoma has slowly increased over the past decades. The Preventive Oncology Academic Award will give me an opportunity to become a competent melanoma molecular epidemiologist. To this end, I will advance my academic understanding of melanoma through further education in the basic sciences, molecular biology/epidemiology, genetics, and clinical decision making. Practical experience will be gained through participation in molecular laboratory biology, with a focus on methodologies used in molecular epidemiology. Two research projects are proposed to explore the association of a candidate susceptibility gene and development of melanoma. Mutations in the candidate gene of interest, the melanocortin-1 receptor (MC1R), may affect melanin synthesis, resulting in an increased potential for cellular DNA damage that may lead to melanocytic carcinogenesis. The goals of the first study are i) to determine the number and types of gene variants among persons with MPM and single cutaneous melanoma (SCM), and ii) to test whether these mutations play a role in the subsequent development of MPM. The results will contribute greatly to the epidemiologic literature on candidate susceptibility genes associated with melanoma and will help focus primary and secondary prevention for persons at increased risk for secondary, primary melanomas. The second project evaluates whether allelic variants in the MC1R gene explain the pattern of melanoma in families prone to melanoma. Result from this project may provide valuable insight into the genetic predisposition to melanoma seen in some families, and may lead to more efficient mechanisms of primary prevention and clinical follow-up within these families.